scholarly journals Mining database for the clinical significance and prognostic value of ESRP1 in skin cutaneous melanoma

2020 ◽  
Author(s):  
Baihe Wang ◽  
Caixia Kou ◽  
Jianfang Sun ◽  
Xiulian Xu

Abstract Background ESRP1 has been described as epithelium-specific splicing regulator involved in many tumors progression. However, the role of ESRP1 in skin cutaneous melanoma is unclear. In the present study, we explored the expression levels of ESRP1 in melanoma and its effect on prognosis and immune infiltration. Methods This study integrated the information from ONCOMINE, GEPIA and UALCAN databases. We explored the genes closely related to ESRP1 using LINKEDIMECS and further analyzed the target kinase, miRNA and transcription factors of ESRP1.GSEA software was used to analyze the changes of GO function enrichment and KEGG pathway after ESRP1 and its related 100 genes changes. Finally, TIMER was used to analyze the relationship between ESRP1 and tumor immune cell infiltration. Results The expression of ESRP1mRNA was significantly downregulated in SKCM patients in comparison with healthy control based on tumor stage and lymph node metastasis status. Low level of ESRP1 expression correlated with better overall survival. ESRP1 is specifically related to tumor-associated kinases CDK1, miRNA138, and transcription factors ETF. Functional network analysis demonstrated that ESRP1 is involved in the regulation of the condensed chromosome, epidermis development, translational initiation, ribosome, drug metabolism, and chemical carcinogenesis. Mechanistically, results suggested that ESRP1 might play an important role in regulating tumor-associated macrophages polarization, DCs infiltration, Treg cells and T cell exhaustion. Conclusion Our study demonstrates ESRP1 expression and its prognostic value and potential regulatory networks in SKCM, shedding light on the clinical significance of ESRP1 and providing a novel biomarker for determining prognosis and immune infiltration in SKCM.

2020 ◽  
Author(s):  
Kai Gan ◽  
Yue Gao ◽  
KuangZheng Liu ◽  
Bin Xu ◽  
Ming Chen

Abstract Objective: Human Epidermal Growth Factor Receptor 2 (HER2) is highly expressed in a variety of tumors and associated with patients’ prognosis, but its role in bladder cancer remains unclear. We conducted this meta-analysis to explore the clinical significance and prognostic value of HER2 in bladder cancer and its potentiality as an immunotherapy target.Methods: PubMed was searched for studies published between January 1, 2000 and January 1, 2020. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were used to investigate the relationship between HER2 and bladder cancer. UALCAN website was used to obtain TCGA (The cancer genome atlas) database.Results: Our study includes 14 articles, 1398 patients. HER2 expression was significantly higher in bladder cancer than in normal tissues. Our meta-analysis results did not reveal any effect of gender on the expression of HER2 levels in bladder cancer patients. However, HER2 expression in male patients was significantly higher than that in women according to TCGA databases. HER2 expression was also associated with carcinoma in situ, multifocal tumors, large tumor size, high tumor stage and grade, lymph node metastases, risk of recurrence and progression, low recurrence-free survival (RFS) rate. HER2 expression status had no effect on overall survival.Conclusions: Our meta-analysis showed that HER2 expression was related to pathological malignancy and poor prognosis in bladder cancer which indicated that it could be used as an effective biomarker and therapeutic target.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaopeng Cai ◽  
Jiaming Zhou ◽  
Jingwen Deng ◽  
Zhi Chen

Abstract Background Epigenetic alterations contribute greatly to metastasis and dissemination in hepatocellular carcinoma (HCC). SMARCC1, as a SWI/SNF chromatin remodeling factor, has been reported to play important roles in many cancers. For the first time, with the bioinformatics analysis and wet-bench experiments, we explored the biological significance of SMARCC1 and its potential as putative therapeutic target in HCC. Methods The mRNA expression profiles and prognostic value of SMARCC1 were analyzed in the Oncomine, UALCAN and Kaplan–Meier Plotter databases. The expression of SMARCC1 and associated clinicopathological factors were further evaluated using a tissue microarray. Differentially expressed genes associated with SMARCC1 in HCC were obtained and analyzed via the LinkedOmics and GEPIA databases and Cytoscape software. To verify the important role of SMARCC1 in HCC, we knocked down and overexpressed SMARCC1 in different hepatic cell lines and conducted several functional experiments. Then, we evaluated the mutation profiles and transcriptional regulators of SMARCC1 using the cBioPortal, COSMIC, CistromeDB and TCGA databases. Finally, we addressed the relationship of SMARCC1 expression with immune cell infiltration via TIMER database analysis. Results Through data mining and tissue microarray verification, we found that the protein and mRNA levels of SMARCC1 are high in tumor tissues, which has remarkable diagnostic value in HCC patients. SMARCC1 and its hub genes showed prognostic value in HCC. Furthermore, we confirmed that SMARCC1 influenced the proliferation, migration, and invasion of HCC cells. Moreover, correlation analyses revealed that SMARCC1 expression was positively correlated with ZBTB40 transcription factors and negatively correlated with the DNA methylation level. Overall, we found that SMARCC1 affects immune infiltration and plays a tumor-promoting role in HCC. Conclusions SMARCC1 is overexpressed and is a putative prognostic predictor in HCC. Due to the tumor-promoting role of SMARCC1, treatments inhibiting DNA methyltransferases and transcription factors or weakening the role of SMARCC1 in immune infiltration might improve the survival of HCC patients.


2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Ding Li ◽  
Shi-Fang Li ◽  
Xiao-Yuan Li ◽  
Xiao-Wei Sun ◽  
Tian-Yue Sun ◽  
...  

Objective. To explore the potential mechanism of Huanglian Jiedu Decoction (HJD) treatment and prevention of metastatic Cutaneous Melanoma (CM) occurrence and metastasis based on network pharmacological methods and immune infiltration analysis. Methods. The GEO database was used to obtain metastatic CM disease targets, the TCMSP database and the HERB database were used to obtain HJD action targets, core genes were screened by protein interaction network, and the potential mechanism of HJD in the treatment of metastatic CM was explored by enrichment analysis, prognostic analysis and immune infiltration analysis. Results. HJD treatment of metastatic CM involved 60 targets, enrichment analysis showed that HJD treatment of metastatic CM involved Chemokine signaling pathway, NF-kappa B signaling pathway, and Fluid shear stress and atherosclerosis, etc. Prognostic analysis revealed that HJD had a certain ability to improve the prognosis of metastatic CM patients. Immune infiltration analysis showed that HJD could inhibit the immune cell infiltration of metastatic CM patients by acting on related targets. Conclusions. Our study identified the potential mechanism of HJD in the treatment of metastatic CM through network pharmacology, and revealed the mechanism of HJD in the prevention of Skin Cutaneous Melanoma metastasis through immune infiltration analysis and prognostic analysis.


2021 ◽  
Author(s):  
Meihua Ru ◽  
Ying-Bo Liu ◽  
Zhi-Hui Tian ◽  
IVAN STEVE GODJE GODJE ◽  
Jian-Qiang Li

Abstract Objective: This study aims to explore the role of aniline-actin binding protein (ANLN) in the prognosis of lung adenocarcinoma (LUAD) and its role in immune infiltration, and to provide new ideas for clinical diagnosis and treatment.Methods: In this study, we applied bioinformatics methods to analyze the expression pattern and prognostic value of ANLN in LUAD ,and confirmed its independent prognostic value through Cox analysis. TIMER was used to evaluate the correlation between ANLN and tumor infiltrating immunity. LinkedOmics was used to study the co-expressed genes and functional networks related to ANLN.The TIMER database was used to analyze the correlation between ANLN co-expressed genes and tumor infiltrating immune cells. Results: ANLN is highly expressed in most cancers. In the TCGA-LUAD cohort, ANLN was highly expressed in LUAD. ANLN was significantly related to the grade , T stage and N stage of patients with LUAD. It was verified in multiple independent queues. The high expression and highly mutation of ANLN predicts poor survival .Multivariate COX analysis showed that ANLN was an independent risk factor for survival . GSEA analysis shows that ANLN regulates cell cycle, and other pathways. The expression of ANLN was significantly correlated with the level of B cell infiltration.Conclusions: ANLN is closely related to the prognosis of patients with LUAD and tumor immune cell infiltration suggesting that ANLN is a key factor regulating the recruitment of immune cells to LUAD and may play an important role in immune.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yumei Fan ◽  
Bing Liu ◽  
Fei Chen ◽  
Zhiyuan Song ◽  
Bihui Han ◽  
...  

Lung cancer has the highest death rate among cancers globally. Hepcidin is a fascinating regulator of iron metabolism; however, the prognostic value of hepcidin and its correlation with immune cell infiltration in lung cancer remain unclear. Here, we comprehensively clarified the prognostic value and potential function of hepcidin in lung cancer. Hepcidin expression was significantly increased in lung cancer. High hepcidin expression was associated with sex, age, metastasis, and pathological stage and significantly predicted an unfavorable prognosis in lung cancer patients. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) results suggested that hepcidin is involved in the immune response. Furthermore, hepcidin expression was positively correlated with the infiltration levels of immune cells and the expression of diverse immune cell marker sets. Importantly, hepcidin may affect prognosis partially by regulating immune infiltration in lung cancer patients. Hepcidin may serve as a candidate prognostic biomarker for determining prognosis associated with immune infiltration in lung cancer.


2021 ◽  
Author(s):  
shitao jiang ◽  
Junwei Zhang ◽  
Yaoge Liu ◽  
Ting Zhang ◽  
Lei Zhang ◽  
...  

Abstract The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family refers to an updated gene family involved in diverse pathophysiological processes. However, the effect exerted by CMTM family members (CMTMs) in hepatocellular carcinoma (HCC) is still elusive. Herein, to elucidate the expression, prognostic value, and immune roles of CMTMs in HCC, a comprehensive bioinformatic analysis was carried out. Our findings showed that CKLF, CMTM1, CMTM3-4, and CMTM7-8 displayed higher mRNA expression levels in HCC tissues than in normal tissues, yet CMTM2, CMTM5, and CMTM6 were lower in HCC tissues. The levels of CMTM1, CMTM2, and CMTM4 were related to tumor stage. Survival analysis showed that high levels of CKLF, CMTM1, CMTM4, and CMTM6-7 were associated with shorter overall survival (OS). Conversely, a high level of CMTM5 in HCC patients was associated with improved OS. We also found that CKLF, CMTM1-4, and CMTM6-7 were closely correlated with immune infiltration in the HCC microenvironment. In conclusion, this study indicates that CMTMs exert a crucial effect on HCC microenvironment remodeling. CKLF, CMTM1, CMTM4, and CMTM6-7 are potential targets of precision therapy, and CMTM5 is a tumor-suppressive gene that was associated with improved survival in HCC patients.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yangyang Zeng ◽  
Yingying Shi ◽  
Lu Xu ◽  
Yulan Zeng ◽  
Xiao Cui ◽  
...  

BackgroundMitochondrial ribosomal protein L15 (MRPL15), a member of mitochondrial ribosomal proteins whose abnormal expression is related to tumorigenesis. However, the prognostic value and regulatory mechanisms of MRPL15 in non-small-cell lung cancer (NSCLC) remain unclear.MethodsGEPIA, ONCOMINE, Gene Expression Omnibus (GEO), UALCAN, Kaplan–Meier plotter, PrognoScan, LinkedOmics and GeneMANIA database were utilized to explore the expression and prognostic value of MRPL15 in NSCLC. Additionally, immune infiltration patterns were evaluated via ESTIMATE algorithm and TISIDB database. Furthermore, the expression and prognostic value of MRPL15 in lung cancer were validated via immunohistochemistry (IHC) assays.ResultsIn NSCLC, multiple cohorts including GEPIA, ONCOMINE and 8 GEO series (GSE8569, GSE101929, GSE33532, GSE27262, GSE21933, GSE19804, GSE19188, GSE18842) described that MRPL15 was up-regulated. Moreover, MRPL15 was notably linked to gender, clinical stage, lymph node status and the TP53 mutation status. And patients with high MRPL15 expression showed poor overall survival (OS), progression-free survival (PFS), disease-free survival (DFS) and relapse-free survival (RFS) in NSCLC. Then, functional network analysis suggested that MRPL15 participated in metabolism-related pathways, DNA replication and cell cycle signaling via pathways involving several kinases, miRNAs and transcription factors. Additionally, it was found that MRPL15 expression was negatively related to immune infiltration, including immune scores, stromal scores and several tumor-infiltrating lymphocytes (TILs). Furthermore, IHC results further confirmed the high MRPL15 expression and its prognostic potential in lung cancer.ConclusionsThese findings demonstrate that high MRPL15 expression indicates poor prognosis in NSCLC and reveal potential regulatory networks as well as the negative relationship with immune infiltration. Thus, MRPL15 may be an attractive predictor and therapeutic strategy for NSCLC.


2021 ◽  
Author(s):  
Yanping Hu ◽  
Yihang Shen

Abstract Background: Colorectal cancer is the third commonest cancer and the second leading cause of cancer deaths globally. The Pre-B-cell leukemia transcription factor (PBX) family plays an essential biological role in the growth and development of the organism. PBX genes have been found to be implicated in the tumorigenesis of a variety of human tumors through multiple pathways, but its function in colorectal cancer is unclear. Methods: The expression pattern, prognostic value and relationship with immune infiltration of PBX genes in patients with colorectal cancer were investigated using the Oncomine, GEPIA, Kaplan-Meier Plotter and TIMER databases. In addition, gene mutation and interaction analysis of PBX family members in colorectal cancer patients using cBioPortal and GeneMANIA databases, respectively.Results: We revealed that a significantly lower expression level of PBX1, PBX2 and PBX3 in colorectal cancer tissues than in normal tissues, and the expression levels of PBX1 and PBX2 were significantly correlated with clinical tumor stage. Furthermore, survival analysis showed that high transcript levels of PBX4 were associated with overall survival in colon cancer patients, while low levels of PBX2 predicted improved disease-free survival in rectal cancer patients. In addition, in colon and rectal cancers, PBX proteins were notably associated with infiltration of multiple immune cells, including CD4+ T cells, CD8+ T cells, macrophages, neutrophils, B cells, and dendritic cells.Conclusion: These findings implies that PBX1 and PBX3 are potential targets for precision therapy of colorectal cancer patients and that PBX2 and PBX4 may be new prognostic markers for colorectal cancer patients.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16256-e16256
Author(s):  
Xianghou Xia ◽  
Yang Yu ◽  
Hongjian Yang ◽  
Dehong Zou ◽  
Canming Wang ◽  
...  

e16256 Background: Although pyroptosis is critical for macrophages against pathogen infection, its role in cancer cells remains elusive. GSDMC is a pyroptosis executioner newly identified in cancer cells and have been shown to facilitate inflammatory tumor death. However, the expression of GSDMC in Pancreatic Ductal Adenocarcinoma (PDAC), its prognostic significance and possible impact on reshaping tumor immune microenviroment in PDAC is still unknown. Methods: We investigated the expression level of GSDMC using TNM plotter with TCGA and GTEx databases, the prognostic value of GSDMC in PDAC using Kaplan-Meier plotter with TCGA, GTEx and TCGA databases. The correlations between GSDMC and immune infiltration in PDAC were calculated using TIMER2.0 and TIDE with TCGA database. We further validated the prognostic value of GSDMC with immunohistochemistry(IHC) staining on a tissue microarray of 172 cases of PDAC patients receiving treatment in our institution. Correlations between expression of GSDMC and tumor infiltration lymphacytes(TILs) cells were also analyzed on tissue samples of those 172 PDAC patients. Results: TNM plotter analysis shows that the expression of GSDMC in PDAC tumor tissue is 10.49 folds higher than it is in pancreatic normal tissues (p = 8.86*e-56). Results from Kaplan-Meier plotter analysis shows high expression of GSDMC is significantly correlated with poorer overall survival(OS), HR = 1.8(1.19−2.71) logrank P = 0.004 and shorter relapse free survival (RFS), HR = 4.6(1.94−10.88), Logrank P = 0.00014 in PDAC. Analysis with TIMER2.0 and TIDE platform shows that expression of GSDMC is positively correlated with immunosuppressive cells, Cancer Associated Fiberblast (CAF) and Meyloid Derived Tumor Suprresso Cells(MDTSC). IHC staining analysis results is also consistent with aformentioned bioinformatic analysis, showing that high GSDMC expression correlated with shorter OS and reduced Tils infiltration. Conclusions: Our findings suggest that high expression of GSDMC is related to poor prognosis and compromised immune cell infiltration in PDAC. GSDMC holds promise for serving as a valuable prognostic marker and therapeutic target in PDAC.


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